Exogenous Hormones, IL-6 and NHL Risk in Women

描述（由申请人提供）：自20世纪40年代以来，非霍奇金淋巴瘤（NHL）的发病率一直在上升。妇女的发病率低于男子，但很少有危险因素可以解释随时间或按性别的发病率模式。一种可能解释男女风险模式差异的暴露是激素治疗（HT）。我们自己之前的研究表明，激素和其他外源性雌激素暴露可降低女性患高度和中度非霍奇金淋巴瘤的风险，但另一项研究结果表明，激素可增加滤泡性非霍奇金淋巴瘤的风险（我们未研究这一亚型）。两项研究对HT-NHL关系的潜在混杂因素的信息有限；然而，这些结果很有趣，因为细胞类型的进化可能取决于b细胞的成熟和分化，而b细胞的成熟和分化受白细胞介素-6 （IL-6）水平的影响；反过来，这些又受到个体IL-6基因型的影响，并可能受到雌激素和孕激素暴露的影响。

DESCRIPTION (provided by applicant): Non-Hodgkin's lymphoma (NHL) rates have been increasing since the 1940s. Incidence is lower among women than among men, yet few risk factors explain incidence patterns over time or by gender. One possible exposure that may explain differences in risk patterns of men and women is hormone therapy (HT). Our own prior research suggested HT and other exogenous estrogen exposures decrease women's risk of high and intermediate NHL, yet results of another study suggest HT increases risk of follicular NHL (a subtype we did not study). Both studies had limited information on potential confounders of an HT-NHL relationship; nevertheless these results are intriguing because the evolution of cell type may depend on B-cell maturation and differentiation which is influenced by levels of interleukin-6 (IL-6); these, in turn, are influenced by the individual's IL-6 genotype and may be impacted by estrogen and progesterone exposure. We propose to conduct a population-based case-control study of B-cell NHL among women 20- 79 years of age, living in Los Angeles County, who are English speaking. We will recruit 1173 cases and 1173 controls, who will provide information during an in-person interview and will provide a buccal cell sample. Cases will have a first primary NHL diagnosis that occurs between July 1, 2004 and December 31, 2007. Controls will be frequency matched to cases by age (5 year age groups) and race/ethnicity and will be identified by surveying the neighborhoods of cases. In this study we will address 1) whether HT use (including specific types, durations, ages and recency of use) affects NHL risk; 2) whether oral contraceptives (including types, durations, and ages of use), lactation suppressants or other exogenous hormones affect NHL risk; 3) whether NHL risk associated with use of exogenous hormones varies by histologic subtype; 4) whether IL-6 genotype (as defined by 4 polymorphisms) modifies any of these relationships; and 5) whether reproductive factors, medical exposures or lifestyle characteristics influence risk of NHL.